PXD029117

PXD029117 is an original dataset announced via ProteomeXchange.

Title	GM1 promotes early Aβ oligomer formation and maintenance
Description	The aggregation of amyloid beta (Aβ) peptide is associated with Alzheimer’s disease (AD) pathogenesis. Cell membrane composition, especially monosialotetrahexosylganglioside (GM1), is known to promote the formation of Aβ fibrils, yet little is known about the roles of GM1 in the early steps of Aβ oligomer formation. Here, by using GM1-contained liposomes as a mimic of neuronal cell membrane, we demonstrate that GM1 is a critical trigger of Aβ oligomerization and aggregation. We find that GM1 not only promotes the formation of Aβ fibrils, but also facilitates the maintenance of Aβ oligomers on liposome membranes. We structurally characterize the Aβ oligomers formed on the membrane and find that GM1 captures Aβ by binding to its arginine-5 residue. To interrogate the mechanism of Aβ oligomer toxicity, we design a new liposome-based Ca2+-encapsulation assay and provide new evidence for the Aβ ion channel hypothesis. Finally, we conduct cell viability assay to determine the toxicity of Aβ oligomers formed on membranes. Overall, by uncovering the roles of GM1 in mediating early Aβ oligomer formation and maintenance, our work provides a novel direction for pharmaceutical research for AD.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:45:44.040.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nikolay Dokholyan
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2021-10-13 22:41:28	ID requested
1	2023-05-10 08:49:19	announced
⏵ 2	2023-11-14 08:45:52	announced	2023-11-14: Updated project metadata.

Zhang DY, Wang J, Fleeman RM, Kuhn MK, Swulius MT, Proctor EA, Dokholyan NV, 42 Oligomer Formation and Maintenance. ACS Chem Neurosci, 13(13):1979-1991(2022) [pubmed]

submitter keyword: oligomers, GM1, Alzheimer's disease,amyloid beta

Nikolay V. Dokholyan
contact affiliation	Department of Pharmacology, Penn State College of Medicine
contact email	dokh@psu.edu
lab head
Nikolay Dokholyan
contact affiliation	Penn State College of Medicine
contact email	dokh@psu.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/05/PXD029117

PRIDE project URI

• PRIDE
  1. PXD029117
     1. Label: PRIDE project
     2. Name: GM1 promotes early Aβ oligomer formation and maintenance